Osteoarthritis-associated basic calcium phosphate crystals induce IL-1β, IL-18 and S100A8 production in a tyrosine kinase dependent manner

Abstract

s / Osteoarthritis and Cartilage 20 (2012) S54–S296 S233 Th2, Th17, Treg) and activation markers. T-cell cytokine secretion (IL-2, IL4, IL-6, IL-10, IL-17A, INF-g, TNF) in SF was measured by cytometric bead array (CBA) analysis. Results: Analysis of PB did not show any significant difference within the OA patient groups and in comparison to controls. In SM a distinct infiltration of CD4+ T-cells was present in all three OA groups, which significantly increasedwith OA stage (p<0.05). Further, CD4+ T-cell subsets in SM and PB samples were analysed. Whereas in PB only a small proportion of CD4+ T-cells were activated and stained positive for the specific subsets, the majority of SM T-cells were differentiated into the T-cell subsets and this increasedwith OA stage (Figure 1). The highest increase wasmeasured for the inflammatory T cell subsets Th1 and Th17, which significantly altered the Th1/Th2 and Th17/Treg balance. Further analysis of activation markers displayed an activated phenotype of CD4+ T-cells in the SM (CD69+, CD45RO+, CD45RA-, CD62L-) but not in PB. CBA analysis confirmed a significant increase of all T-cell cytokines in the SF of OA groups 2 and 3 when compared to group 1 (p<0.05). Between group 2 and 3, pro-inflammatory Th1 and Th17 cytokines (TNF and IL-17) were further increased and anti-inflammatory Th2 and Treg cytokines (IL-4, IL-10) decreased in group 3. IL-2, IL-6 and INF-g were slightly higher in group 2. Conclusions: In contrast to SM, no differences were observed between the PB samples of OA patients and controls, showing that the relevant role of inflammatory cells in OA remains a local process. The infiltration of OA synoviumwith inflammatory cells is not solely a phenomenon of late stage OA. In fact, CD4+ T-cells are already present and activated in the affected joints of early OA stages. T-cell infiltration and polarisation correlates with OA disease stages and shifts the Th1/Th2 and Th17/Treg balance towards an inflammatory T-cell phenotype. Thus, onset and progression of OA is accompanied by an increasing influx of CD4+ T-cells into the SM, their activation, cytokine production and polarisation. These results underline the relevance of T-cells in the inflammatory process of OA, not only in latestage disease but also in early OA stages. In “classical” inflammatory joint diseases such as rheumatoid arthritis we know that T-cell derived inflammation contributes to cartilage degeneration and joint destruction. The role of these cells in OA needs to be further studied. Nevertheless our current results suggest that T-cell activation and polarisation may play a role in both the initiation and progression of OA, and as such provide a potential therapeutic target.